Protective to a T: The Role of T Cells during Zika Virus Infection

Pardy, Ryan D.; Richer, Martin J.

doi:10.3390/cells8080820

Cited by 29 publications

(26 citation statements)

References 66 publications

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“…Vaccine-induced T cell responses likely also contribute to protection against transplacental infection, although the required phenotypes and their contributions in different model systems remain to be fully elucidated [ 48 ]. Induction of T cell responses by the chimeric BinJV vaccines also remains to be characterized, although wild-type mice rather than IFNAR −/− mice are being used for these studies, given the roles of type I IFNs in T cell biology [ 12 , 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

A Zika Vaccine Generated Using the Chimeric Insect-Specific Binjari Virus Platform Protects against Fetal Brain Infection in Pregnant Mice

et al. 2020

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Zika virus (ZIKV) is the etiological agent of congenital Zika syndrome (CZS), a spectrum of birth defects that can lead to life-long disabilities. A range of vaccines are in development with the target population including pregnant women and women of child-bearing age. Using a recently described chimeric flavivirus vaccine technology based on the novel insect-specific Binjari virus (BinJV), we generated a ZIKV vaccine (BinJ/ZIKA-prME) and illustrate herein its ability to protect against fetal brain infection. Female IFNAR−/− mice were vaccinated once with unadjuvanted BinJ/ZIKA-prME, were mated, and at embryonic day 12.5 were challenged with ZIKVPRVABC59. No infectious ZIKV was detected in maternal blood, placenta, or fetal heads in BinJ/ZIKA-prME-vaccinated mice. A similar result was obtained when the more sensitive qRT PCR methodology was used to measure the viral RNA. BinJ/ZIKA-prME vaccination also did not result in antibody-dependent enhancement of dengue virus infection or disease. BinJ/ZIKA-prME thus emerges as a potential vaccine candidate for the prevention of CSZ.

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Section: Discussionmentioning

confidence: 99%

A Zika Vaccine Generated Using the Chimeric Insect-Specific Binjari Virus Platform Protects against Fetal Brain Infection in Pregnant Mice

et al. 2020

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“…Macaque models have begun to show the importance of innate and adaptive responses in controlling infection, so our goal was to provide an additional descriptive account of immune responses that occur following infection with a Brazilian ZIKV strain. We also asked whether CD8 T cells have a role in controlling infection, owing to the importance of these cells in providing protection in mouse models 4 – 6 .…”

Section: Discussionmentioning

confidence: 99%

“…The immunology of ZIKV infection has been most extensively studied in mice, and murine studies have shown the critical importance of type-I interferon (IFN) in limiting disease together with the protective roles of humoral and T cell responses 4 – 7 . A growing body of literature also describes immune responses following ZIKV infection in nonhuman primates (NHPs), which are often used in preclinical vaccine studies 8 given their genetic and immunologic similarities to humans.…”

Section: Introductionmentioning

confidence: 99%

Immune outcomes of Zika virus infection in nonhuman primates

Schouest

Fahlberg

Scheef

et al. 2020

Sci Rep

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Although the Zika virus (ZIKV) epidemic is subsiding, immune responses that are important for controlling acute infection have not been definitively characterized. Nonhuman primate (NHP) models were rapidly developed to understand the disease and to test vaccines, and these models have since provided an understanding of the immune responses that correlate with protection during natural infection and vaccination. Here, we infected a small group of male rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques with a minimally passaged Brazilian ZIKV isolate and used multicolor flow cytometry and transcriptional profiling to describe early immune patterns following infection. We found evidence of strong innate antiviral responses together with induction of neutralizing antibodies and T cell responses. We also assessed the relative importance of CD8 T cells in controlling infection by carrying out CD8 T cell depletion in an additional two animals of each species. CD8 depletion appeared to dysregulate early antiviral responses and possibly increase viral persistence, but the absence of CD8 T cells ultimately did not impair control of the virus. Together, these data describe immunological trends in two NHP species during acute ZIKV infection, providing an account of early responses that may be important in controlling infection. Zika virus (ZIKV) has been a known pathogen for over half a century 1, but severe disease manifestations were not directly associated with the virus for most of its history. The recent outbreaks of ZIKV in the Western hemisphere became linked to neurologic and congenital syndromes that have provided strong incentives to develop prophylactic and therapeutic countermeasures. Several vaccine candidates spanning multiple platforms have performed well in preclinical studies and have advanced to clinical trials, but the waning of the epidemic has precluded efficacy testing in large populations 2,3. Additionally, an understanding of the immune responses that provide protection during natural infection is not yet complete, which also complicates our ability to evaluate whether vaccines will replicate these protective responses. The immunology of ZIKV infection has been most extensively studied in mice, and murine studies have shown the critical importance of type-I interferon (IFN) in limiting disease together with the protective roles of humoral and T cell responses 4-7. A growing body of literature also describes immune responses following ZIKV infection in nonhuman primates (NHPs), which are often used in preclinical vaccine studies 8 given their genetic and immunologic similarities to humans. Multiple species of macaques have been utilized, and these models replicate clinical aspects of viral infection and disease 9-13. However, the relative importance of innate and adaptive responses in controlling infection in monkeys is only beginning to be explored in depth, and this data is an important open question for the evaluation of candidate vaccines. Here, we carried out a descriptive anal...

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“…The humoral and cellular immune responses influence ZIKV pathogenesis and play key roles in controlling ZIKV replication [45]. In particular, neutralizing antibodies, induced by ZIKV vaccines, may block infection [27,46], while CD4 + and CD8 + T cells secrete IFN-γ, IL2 (Th1), IL-4, and IL-5 (Th2) cytokines to further promote antibody production or directly kill infected cells [47][48][49][50]. CD8 + T cells are critical for protection against ZIKV infection in mice, non-human primates, and humans [45,48,[50][51][52].…”

Section: Discussionmentioning

confidence: 99%

Effects of Adjuvants on the Immunogenicity and Efficacy of a Zika Virus Envelope Domain III Subunit Vaccine

et al. 2019

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Zika virus (ZIKV), a mosquito-borne flavivirus, has attracted global attention due to its close association with congenital Zika syndrome and neurological diseases, and transmission through additional routes, such as sexual contact. Currently there are no vaccines approved for ZIKV, and thus, there is an urgent need to develop an effective and safe ZIKV vaccine. Domain III (DIII) of the ZIKV envelope (E) protein is an important vaccine target, and a vaccine developed using a mutant DIII of E (EDIII) protein protects adult and pregnant mice, and unborn offspring, against ZIKV infection. Here, we have used immunocompetent BALB/c mice treated with anti-interferon-α/β receptor 1 (Ifnar1) antibodies to investigate whether three adjuvants (aluminum (Alum), monophosphoryl lipid A (MPL), and MF59), either alone or in combination, could improve the efficacy of this EDIII subunit vaccine. Our data show that, although vaccine formulated with a single adjuvant induced a specific antibody and cellular immune response, and reduced viral load in mice challenged with ZIKV, the combination of Alum and MPL adjuvants led to a more robust and balanced immune response, stronger neutralizing activity against three recent ZIKV human strains, and greater protection against a high-dose ZIKV challenge. Particularly, the combination of Alum with MPL significantly reduced viral titers and viral RNA copy numbers in sera and tissues, including the male reproductive organs. Overall, this study has identified the combination of Alum and MPL as the most effective adjuvant for ZIKV EDIII subunit vaccines, and it has important implications for subunit vaccines against other enveloped viruses, including non-ZIKV flaviviruses.Vaccines 2019, 7, 161 2 of 16 with microcephaly, fetal demise, and other congenital disorders [4][5][6]. Thus, ZIKV has emerged as a global health threat and there is an urgent requirement for an effective vaccine to combat ZIKV-associated diseases.The ZIKV genome encodes a single polyprotein, which is processed into three structural proteins (capsid (C), precursor of membrane/membrane (prM/M), and envelope (E)) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) [7][8][9]. The E protein has important roles in infection and pathogenesis, is involved in virus binding to target cells and membrane fusion, and also serves as an important vaccine target [7,8]. The E protein is a transmembrane protein and consists of three domains termed I, II, and III (DI-DIII), a fusion loop (FL), and a stalk region (S) [8]. The DI-DII region of ZIKV E protein is a target for cross-reactive antibodies with other flaviviruses, such as dengue virus (DENV) and West Nile virus (WNV), whereas the DIII domain induces ZIKV-specific antibodies [10][11][12], and therefore, is a key target for ZIKV vaccine development. ZIKV vaccine candidates under development include inactivated virus, live attenuated virus, DNA, mRNA, viral vectors, virus-like particles (VLPs), and viral proteins (or subunit vaccines) [13][14][15][16]. Although ma...

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Protective to a T: The Role of T Cells during Zika Virus Infection

Cited by 29 publications

References 66 publications

A Zika Vaccine Generated Using the Chimeric Insect-Specific Binjari Virus Platform Protects against Fetal Brain Infection in Pregnant Mice

A Zika Vaccine Generated Using the Chimeric Insect-Specific Binjari Virus Platform Protects against Fetal Brain Infection in Pregnant Mice

Immune outcomes of Zika virus infection in nonhuman primates

Effects of Adjuvants on the Immunogenicity and Efficacy of a Zika Virus Envelope Domain III Subunit Vaccine

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